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Background Lymphedema may disrupt local function and affect quality of life (QOL) in patients with head and neck cancer. The purpose of this study was to examine the associations among severity of internal and external lymphedema, symptoms, functional status, and QOL in patients with head and neck cancer. Methods The sample included 103 patients who were ≥3 months after head and neck cancer treatment. Variables assessed included severity of internal and external lymphedema, physical/psychological symptoms, functional status, and QOL. Results Severity of internal and external lymphedema was associated with physical symptoms and psychological symptoms. Patients with more severe external lymphedema were more likely to have a decrease in neck left/right rotation. The combined effects of external and internal lymphedema severity were associated with hearing impairment and decreased QOL. Conclusions Lymphedema severity correlates with symptom burden, functional status, and QOL in patients after head and neck cancer treatment. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Background The prevalence, severity, and functional implications of adverse oral health outcomes attributed to head and neck cancer therapy are largely undefined. We report development of an oral health outcome subscale for the Vanderbilt Head and Neck Symptom Survey (VHNSS). Methods Oral health outcome questions were formulated through literature review and consultation with an expert panel. Questions were incorporated into the VHNSS resulting in a 50-item survey, scored 0 (none) to 10 (severe). The tool was administered to 70 subjects who completed radiation to assess for feasibility. Results Patient acceptance was high with a completion time <10 minutes. A full range of scores was noted for 46 of 50 questions. Oral health symptom burden was high early and late posttreatment. Conclusions The VHNSS version 2.0 was feasible and could be completed in a timely manner. Validation studies are ongoing. The high prevalence of adverse oral health outcomes warrants further study. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 [ABSTRACT FROM AUTHOR]

Background. We describe the development and validation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), which was designed to screen for tumor- and treatment-specific symptoms in patients with head and neck cancer undergoing concurrent chemoradiation (CCR). Methods. Using a 2-step card sort method, we identified high-impact and high-frequency toxicities in patients with head and neck cancer treated with CCR. This resulted in a 28-item questionnaire which scores symptoms on a 0 to 10 scale (none to severe). The tool was validated using data collected from 5 supportive care studies comprising a total sample of 332 patients with head and neck cancer. Results. Responses to the VHNSS items demonstrated a very consistent pattern (Cronbach's alpha = 0.943) with each item contributing substantially to the global index. Five symptom subscales were identified including “Nutrition,” “Pain,” “Voice,” “Swallow,” and “Mucous/Dry Mouth.” Each of the cluster scores demonstrated good internal consistency. The pattern of associations between the VHNSS and established tools indicated appropriate convergence and divergence. Comparison of global and subscale scores and objective measure were also in the expected direction providing further evidence of validity. Conclusions. The findings provide support that the VHNSS is a valid and reliable tool to assess head and neck–specific symptom burden and function loss. Further research to evaluate this screening tool as a part of a systems approach to supportive care is warranted. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

The article focuses on the influence of clinical manifestations, grading, and management of infusion reaction (IR) in cancer clinical trials based on U.S. and European perspectives. It notes that monoclonal antibodies do not have overlapping side effects with cytotoxic agents in general, however, severe IR has been reported. It states that geographic factors in the incidence of IR are evident. It points out that clinicians must understand risk and recognize signs and symptoms in order to manage IR.

We identified 35 patients who had undergone stereotactic radiosurgery (SRS) for their biochemically proven Cushing's disease in order to assess the efficacy of SRS with regard to control of hypercortisolism, improvement of clinical features and prevention of tumor progression, and subsequent incidence of hypopituitarism. Seventeen (49%) patients achieved control of their cortisol levels following SRS; the mean time to normalization was 7.5 months (range: 1-33). Four (19%) patients experienced recurrent hypercortisolism at a mean time of 35.5 months following therapy (range: 17-64). Control of tumor progression was achieved in 91% patients. Fourteen (40%) patients demonstrated a new pituitary deficiency following SRS. Our results suggest that cortisol levels are normalized more efficiently and with a lower recurrence rate with SRS than with conventional fractionated external beam radiotherapy (EBT). We have confirmed the near 100% tumor control rate reported with SRS. The percentage of patients developing pituitary insufficiency following SRS is less than that of patients having undergone EBT; however, deficits occurred up to 10 years posttreatment. We advocate the use of SRS as the primary therapeutic modality in those patients who are poor surgical candidates, or as the adjunct treatment to microsurgery in eliminating residual tumor cells or disease that is not easily amenable to resection. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. The management of craniopharyngiomas has historically been controversial in terms of the extent of initial surgical resection and the use of additional treatments. Various options include radical excision versus a more conservative surgical approach followed by external beam radiation; most recently, intracystic 32 P radiation has been used in selected patients. Methods. We reviewed our experience with 25 patients with craniopharyngiomas treated between 1984 and 1999 to assess the effectiveness of external beam radiation and intracystic 32 P radiation therapy in preventing progression and recurrence of local disease. Results. All patients underwent surgery as a component of initial therapy for their histologically-proven craniopharyngiomas. Fifteen patients additionally received external beam radiation. Forty-five percent of patients who underwent incomplete resections followed by external beam radiation required additional therapy. In contrast, 80% of patients who had incomplete resections without post-operative external beam radiation required further treatment. Seven patients had intracystic 32 P colloid injections. Neither of the two patients receiving 32 P intracystic radiation as part of their initial therapy needed further treatment. Only one of the five patients receiving 32 P intracavitary radiation for disease progression following initial therapy required further intervention. Of the remaining four patients, three enjoyed responses to treatment and one had stable disease. Conclusions. Our observations support the use of external beam radiation for prevention of tumor progression in adults unable to receive a complete surgical resection. Our results additionally suggest that intracystic 32 P radiation results in control of cystic components of craniopharyngiomas in the majority of cases. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative condition in which clinical symptoms are highly correlated with the loss of glutamatergic synapses. While later stages of AD are associated with markedly decreased glutamate levels due to neuronal loss, in the early stages, pathological accumulation of glutamate and hyperactivity contribute to AD pathology and cognitive dysfunction. There is increasing awareness that presynaptic dysfunction, particularly synaptic vesicle (SV) alterations, play a key role in mediating this early‐stage hyperactivity. In the current study, we sought to determine whether the 3xTg mouse model of AD that exhibits both beta‐amyloid (Aβ) and tau‐related pathology would exhibit similar presynaptic changes as previously observed in amyloid or tau models separately. Hippocampal cultures from 3xTg mice were used to determine whether presynaptic vesicular glutamate transporters (VGlut) and glutamate are increased at the synaptic level while controlling for postsynaptic activity. We observed that 3xTg hippocampal cultures exhibited increased VGlut1 associated with an increase in glutamate release, similar to prior observations in cultures from tau mouse models. However, the SV pool size was also increased in 3xTg cultures, an effect not previously observed in tau mouse models but observed in Aβ models, suggesting the changes in pool size may be due to Aβ and not tau. Second, we sought to determine whether treatment with troriluzole, a novel 3rd generation tripeptide prodrug of the glutamate modulator riluzole, could reduce VGlut1 and glutamate release to restore cognitive deficits in 8‐month‐old 3xTg mice. Treatment with troriluzole reduced VGlut1 expression, decreased basal and evoked glutamate release, and restored cognitive deficits in 3xTg mice. Together, these findings suggest presynaptic alterations are early events in AD that represent potential targets for therapeutic intervention, and these results support the promise of glutamate‐modulating drugs such as troriluzole in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Purpose To report on radiosurgery delivery positioning accuracy in the treatment of tremor patients with frameless image guided radiosurgery using the linear accelerator (LINAC) based ExacTrac system and to describe quality assurance (QA) procedures used. Methods and materials Between 2010 and 2015, 20 patients underwent radiosurgical thalamotomy targeting the ventral intermediate nucleus for the treatment of severe tremor. The median prescription dose was 140 Gy (range, 120-145 Gy) in a single fraction. The median maximum dose was 156 Gy (range, 136-162 Gy). All treatment planning was performed with the iPlan system using a 4-mm circular cone with multiple arcs. Before each treatment, QA procedures were performed, including the imaging system. As a result of the extremely high dose delivered in a single fraction, a well-defined circular mark developed on the posttreatment magnetic resonance imaging (MRI). Eight of these 20 patients were selected to evaluate treatment localization errors because their circular marks were available in posttreatment MRI. In this study, the localization error is defined as the distance between the center of the intended target and the center of the posttreatment mark. Results The mean error of distance was found to be 1.1 mm (range, 0.4-1.5 mm). The mean errors for the left-right, anteroposterior, and superoinferior directions are 0.5 mm, 0.6 mm, and 0.7 mm, respectively. Conclusions The result reported in this study includes all tremor patients treated at our institution when their posttreatment MRI data were available for study. It represents a direct confirmation of target positioning accuracy in radiosurgery with a LINAC-based frameless system and its limitations. This level of accuracy is only achievable with an appropriate QA program in place for a LINAC-based frameless radiosurgery system. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue including an article, which offers a review of the mechanisms and symptoms of hypersensitivity, and another article on how the clinical manifestations, grading and management of reactions are influencing the development of cancer clinical trials.

Purpose: Effective treatment options for refractory depression are needed. Recent advancements permit both precise ablative radiation and functional neurologic connectome analysis using standard magnetic resonance imaging. We combined these innovations to perform stereotactic radiosurgical capsulotomy for the treatment of medically refractory major depressive disorder and study connectome response using a novel tractography-based approach.Methods and Materials: Patients with medically refractory depression were enrolled on a prospective pilot single-arm observational trial from 2020 to 2021 at a single academic tertiary referral center. Bilateral ablation of the anterior limb of the internal capsule was accomplished by mask-based linear accelerator stereotactic radiosurgery. Beck's Depression Inventory measured efficacy. Montreal Cognitive Assessment evaluated cognition.Results: Three patients were enrolled. Depression burden was improved by 88% at 12-month follow-up and by 55% at 18-month follow-up for patient 1 and 2, respectively. Patient 1 discontinued ketamine therapy, and patient 2 discontinued electroconvulsive therapy. Patient 3 reported global improvement in symptoms and function at 3 months. All 3 patients had reduction or resolution of suicidal ideation. No patient experienced cognitive decline or neurologic toxicity, and Montreal Cognitive Assessment score, as well as subjective patient-reported evaluations of concentration and attention, were superior after treatment. Tractography confirmed intended disruption of the cortico-striatal-thalamo-cortical loop with structural reorganization in the connectome. Connectome change was consistent between patients. Observed increases in caudate and putamen connectivity and decreases in thalamic connectivity may explain improved concentration, attention, and depression. The diversity and magnitude of connectome change may correlate with degree of clinical response.Conclusions: In 3 patients with refractory depression, radiosurgical capsulotomy significantly reduced the burden of depression. Functional connectome reorganization offers neurobiological evidence to support further investigations of the role of radiosurgery in depression. [ABSTRACT FROM AUTHOR]

Purpose/objective: Linear accelerator (LINAC) based stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is delivered with cone or multileaf collimators (MLCs), and favorable dosimetry is associated with reduced radionecrosis in normal brain tissue. This study aims to determine whether cones or MLCs has better dosimetric characteristics, to predict differences in toxicity. Methods: All patients treated for AVMs using LINAC SRS from 2003-2017 were examined retrospectively. Demographic data, volumes of normal tissue exposed to 12Gy (V12Gy[cc]) and 4Gy (V4Gy[cc]), maximal dose, and dose gradient were analyzed. Univariate and multivariate analyses were used to evaluate relationships between collimator type, dosimetric parameters, and toxicity. Propensity score matching was used to adjust for AVM size. Results: Compared to MLC, cones were independently associated with reduced V12Gy[cc] after propensity score matching (p=0.008) and reduced neurotoxicity (p=0.016). Higher V12Gy[cc] (p=0.0008) and V4Gy[cc] (p=0.002) were associated with increased neurotoxicity. Conclusions: Treating AVMs with cone-based SRS over MLC-based SRS may improve dosimetry and reduce toxicities. [ABSTRACT FROM AUTHOR]

Purpose: Lymphedema and fibrosis (LEF) are common yet overlooked late effects of head and neck cancer and its therapy. Lack of reliable and valid measures of head and neck LEF is a critical barrier to the timely identification and management of head and neck LEF. To fill this gap, we developed and pilot tested a 64-item patient-reported outcome measure ( Lymphedema Symptom Intensity and Distress Survey-Head and Neck, LSIDS-H&N). This article aims to report the process of further validation and refinement of the tool.Methods and Materials: A prospective, longitudinal study was conducted, and 120 patients with oral cavity and oropharyngeal cancer were recruited. Participants completed the LSIDS-H&N at pretreatment, end of treatment, and every 3 months up to 12 months after treatment. SAS PROC VARCLUS was used to generate preliminary clusters of item responses. Internal consistency of the item responses within each cluster was assessed using Cronbach's alpha.Results: A total of 117 patients completed the study. The participants reported that the LSIDS-H&N was easy to understand and captured their symptoms and medical conditions. However, >50% of participants indicated that the survey was burdensome due to length. Thus, we proceeded with item reduction, and the shortened tool (33-item) was named Head and Neck Lymphedema and Fibrosis Symptom Inventory (HN-LEF Symptom Inventory). The subsequent exploration of symptom clusters identified 7 symptom domain clusters (eg, soft tissue and neurologic toxicity), all of which demonstrated good internal consistency.Conclusions: The HN-LEF Symptom Inventory has been carefully developed and refined to allow clinicians and researchers to capture LEF-associated symptom burden and function impairments. Additional rigorous psychometric testing of the tool is ongoing to further validate the strength and internal validity of this tool. [ABSTRACT FROM AUTHOR]

De-intensification strategies for locally advanced p16+ OPSCC are under active investigation, including omission of contralateral neck radiation (RT) for well-lateralized T1-2N0-2a. This study evaluates the outcomes of omitting contralateral neck nodal levels for p16+ OPSCC that are not well-lateralized. A retrospective review was done of 134 consecutive patients with non-metastatic p16+ OPSCC that were not well-lateralized (< 1 cm from midline or ≥ 1 cm extension to soft palate or base of tongue) who were treated with definitive chemoradiation from 2013 to 2019. IMRT to an EQD2 6364-6735 cGy (200-220 cGy per fraction) was used to treat the primary tumor and ipsilateral or bilateral neck, with tailored nodal level coverage and dose, and with concurrent paclitaxel and carboplatin. Contralateral neck RT was tailored in 121 patients: omitted in 11, limited to level II in 9, and limited to level II and III in 101 (contralateral lower neck omitted); the remaining 13 had bilateral level II-IV neck RT. Local and regional recurrences were evaluated. Median follow up was 45.34 months. Local and/or regional recurrence was noted in 9/134 (6.7%). 3 (2%) recurred in the contralateral neck in unirradiated tissue (out-of-field). All three were salvaged. The remaining 6 recurrences (4%) were in-field; one was at the primary site and 5 were nodal (all ipsilateral). 4 of the 5 regional recurrences were in a location that was treated to EQD2 7000 cGy (all had PET avid nodal disease upfront that was included in the high dose level); the other region of recurrence was treated to an EQD2 6353 cGy (the only recurrence in a never smoker). 4 of the 5 neck recurrences underwent neck dissection; one further underwent adjuvant RT to 5940 cGy in 33 fractions and remains disease-free. 2 of those who underwent salvage neck dissection alone subsequently developed distant metastases. The majority of first recurrences were distant, 19.4% (26/134). 3-year progression free survival (PFS) was 74.41% (95% CI, 65.63-81.26). Taken together, regional recurrence rate in the contralateral, unirradiated neck was 2.5% (3/121) and ultimate locoregional control was 99% (132/134). Our tailored approach demonstrates a contralateral neck local control of 97.5% (118/121) regardless of tumor lateralization; those who recurred in unirradiated cervical lymph nodes were successfully salvaged. Limiting this analysis is moderate sample size and retrospective nature, but it raises important alternative de-escalation strategies (RT volume reduction) for p16+ OPSCC aside from dose reduction, which is under active investigation in phase II/III trials. Improved systemic therapies are needed to combat distant metastases. Prospective randomized clinical trials are needed for further evaluation of nodal omission for definitive chemoradiation of non-well-lateralized p16+ OPSCC. [ABSTRACT FROM AUTHOR]

Standard therapy for locally advanced p16+ OPSCC with cisplatin and bilateral nodal RT results in substantial acute and late toxicities. De-intensification strategies are under active investigation, including the de-escalation of RT dose and field size and use of less toxic RT sensitizing agents. We present our single-institution experience with definitive chemoRT using weekly carboplatin and paclitaxel and modified RT. A retrospective review of 139 consecutive patients with non-metastatic p16+ OPSCC treated with definitive chemoRT from 2013 to 2019 was performed. IMRT dose ranged from 60 to 70 Gy (median 69.96 Gy) to gross disease and 44 to 59.4 Gy (median 54.45 Gy) to elective nodal sites. Modified RT included dose reduction from 70 Gy EQD 2 to 60-67.8 Gy EQD 2 (2.0-2.2 Gy/fraction) and/or field modified contralateral neck. All patients received concurrent weekly paclitaxel (30 mg/m2) and carboplatin (AUC 1); 34 (24.5%) received induction chemotherapy. Patients were classified as low or intermediate risk based on HPV status, smoking history, and nodal staging per RTOG 0129 risk stratification. OS, local and regional RFS, and DSS were estimated using Kaplan-Meier method. Median FU was 40.5 months. Of 139 pts, 96 were low and 43 were intermediate risk. Median age 61 yrs (range, 40-81 yrs). 125 pts were male and 14 were female. TNM staging: 29 pts (20.9%) were T1 (22 N1, 7 N2), 68 (48.9%) T2 (4 N0, 52 N1, 12 N2), 27 (19.4%) T3 (5 N0, 15 N1, 7 N2), and 15 (10.8%) T4 (2 N0, 2 N1, 10 N2, 1 N3). Median smoking history of 22.5 pack-yrs (range, 0.25-150 pack-yrs); 59 never smoked. LR recurrence was noted in 6/96 (6.3%) low risk and 7/43 (16.3%) intermediate risk pts. DM developed in 11/96 (11.5%) low risk and 8/43 (18.6%) intermediate risk pts. Synchronous LR recurrence and DM were noted in 1/96 (1%) low risk and 2/43 (4.7%) intermediate risk pts. The 3-year LRC was 93.6% (95% CI, 86.3-97.1) in the low-risk and 77.8% (95% CI, 61.4-87.8) in the intermediate-risk group. The 3-year OS was 95.4% (95% CI, 88.3-98.3) in the low-risk and 77.6% (95% CI, 61.3 to 87.7) in the intermediate-risk group. The 3-year DSS was 96.6% (95% CI, 89.7-98.9) in the low-risk and 86.8% (95% CI, 71.0-94.3) in the intermediate-risk group. Definitive chemoRT for p16+ OPSCC with concurrent carboplatin and paclitaxel and a modified RT regimen designed to minimize acute and late effects of therapy demonstrated comparable outcomes to standard cisplatin-based chemoRT, such as report on RTOG 0129, with a high rate of LRC at 3 years. Our analysis suggests a role for a less intensive regimen using paclitaxel and carboplatin as a less toxic, effective alternative to cisplatin in the curative management of p16+ OPSCC, particularly in low-risk patients. Strategies for combating distant metastases are needed. Toxicity analysis planned to be presented separately. [ABSTRACT FROM AUTHOR]

Introduction: Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC).Material and Methods: Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) every 21days as IC. Afatinib was started at a dose of 20mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40mg/m(2) weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0.Results: Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities.Conclusions: The MTD of afatinib given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) is 20mg daily. Combination of afatinib at doses higher than 20mg with carboplatin and paclitaxel should be administered with caution due to the toxicities. [ABSTRACT FROM AUTHOR]

Purpose: Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes.Methods and Materials: A total of 410 analyzable patients who had high-risk resected head-and-neck cancers were prospectively randomized to receive either radiation therapy (RT: 60 Gy in 6 weeks) or identical RT plus cisplatin, 100 mg/m(2)i.v. on days 1, 22, and 43 (RT + CT).Results: At 10 years, the local-regional failure rates were 28.8% vs 22.3% (P=.10), disease-free survival was 19.1% vs 20.1% (P=.25), and overall survival was 27.0% vs 29.1% (P=.31) for patients treated by RT vs RT + CT, respectively. In the unplanned subset analysis limited to patients who had microscopically involved resection margins and/or extracapsular spread of disease, local-regional failure occurred in 33.1% vs 21.0% (P=.02), disease-free survival was 12.3% vs 18.4% (P=.05), and overall survival was 19.6% vs 27.1% (P=.07), respectively.Conclusion: At a median follow-up of 9.4 years for surviving patients, no significant differences in outcome were observed in the analysis of all randomized eligible patients. However, analysis of the subgroup of patients who had either microscopically involved resection margins and/or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy. The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT. [ABSTRACT FROM AUTHOR]

CONTEXT: Because surgery, radiation, and/or chemotherapy disrupt lymphatic structures, damage soft tissue leading to scar tissue formation and fibrosis, and further affect lymphatic function, patients with head and neck cancer may be at high risk for developing secondary lymphedema. Yet, no published data are available regarding the prevalence of secondary lymphedema after head and neck cancer treatment. OBJECTIVES: The aim of this study was to examine prevalence of secondary lymphedema in patients with head and neck cancer. METHODS: The study included 81 patients with head and neck cancer who were three months or more post-treatment. External lymphedema was staged using Foldi's lymphedema scale. Internal lymphedema was identified through a flexible fiber-optic endoscopic or mirror examination. Patterson's scale was used to grade degrees of internal lymphedema. RESULTS: Of the 81 patients, 75.3% (61 of 81) had some form of late-effect lymphedema. Of those, 9.8% (6 of 61) only had external, 39.4% (24 of 61) only had internal, and 50.8% (31 of 61) had both types. CONCLUSION: Lymphedema is a common late effect in patients with head and neck cancer, and it develops in multiple external and internal anatomical locations. During physical examination and endoscopic procedures, clinicians should assess patients with head and neck cancer for late-effect lymphedema. Referral for treatment should be considered when lymphedema is noted. Research is needed to examine risk factors of lymphedema in patients with head and neck cancer and its effects on patients' symptoms, function, and quality of life.Copyright © 2012 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. Methods and Materials: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose–volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m2) and carboplatin area under the curve-1 were given concurrently with IMRT. Results: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). Conclusions: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended. [Copyright &y& Elsevier]

Synovial sarcoma is typically an aggressive malignant tumor of the soft tissues, usually in the extremities, that affects young adults. Tumors of the head and neck are rare. Reported head and neck sites have included the hypopharynx (the most common site), the oropharynx, the larynx, and the soft tissues of the neck; only 4 cases of orbital involvement have been previously reported. We describe a case of synovial sarcoma of the medial canthus, which we discovered during a review of a tumor registry. The patient, an 18-year-old woman, underwent conservative excision and postoperative radiation therapy. Long-term follow-up detected no evidence of recurrence. Because there is no established, consistent approach to the treatment of synovial sarcoma of the head and neck, we also present a consensus management plan based on our review of the literature. [ABSTRACT FROM AUTHOR]

Background: Our previous study has shown that nuclear factor-kappa B (NF-κB)-signaling pathway was associated with a higher rate of recurrence in head and neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-κB inhibitor by inhibition of proteasomes, plus docetaxel was assessed for efficacy and toxicity. [ABSTRACT FROM PUBLISHER]

Abstract: The treatment paradigm for locally advanced head and neck cancers has evolved over the past two decades as the role of chemotherapy has been substantiated by clinical trials. Presently, concurrent chemoradiation is considered a standard treatment option for patients with resectable head and neck tumors desiring an organ preservation approach, as well as for patients with locally advanced nasopharyngeal cancers and patients in the postoperative setting who are at high risk for recurrence. The addition of a taxane to induction chemotherapy appears to improve efficacy over cisplatin and 5-FU. Targeted biologic therapies such as the monoclonal antibody Cetuximab has demonstrated efficacy with radiation that appear comparable to chemoradiation combinations and has a favorable toxicity profile. This review will discuss key clinical trials supporting the current standard of care. Emerging new technologies such as intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) will also be reviewed. Functional assessments and quality of life issues will be addressed. [Copyright &y& Elsevier]

Abstract: RTOG 95-02 assessed patient tolerance to hypoxic cell radiosensitizer, etanidazole (SR-2508), combined with radiosurgery. Patients had primary or metastatic brain tumors and previously localized or whole brain irradiation. The toxicity is reported in three groups of patients according to the tumor size. Etanidazole doses of 12g/m2 combined with radiosurgery were well tolerated. [Copyright &y& Elsevier]

Background The improved prognosis for patients with human papillomavirus (HPV)—positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. Methods We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Results Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P= .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [95% CI = 87% to 100%] vs 62% [95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P= .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. Conclusion For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the addition of recombinant human erythropoietin (Epo) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: Eligible patients had SCCHN, with a plan for continuous-course definitive radiotherapy (66–72 Gy) with or without chemotherapy. Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and/or accelerated fractionation radiotherapy. Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL (12.5 g/dL for women). Patients randomized to Epo received 40,000 U once weekly, starting 7–10 days before start of radiotherapy. Results: A total of 148 patients were enrolled; 141 were evaluable. Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm, compared with an average 0.24 g/dL decrease in the control arm (p = 0.0001). Median follow-up was 2.5 years (3.1 years for surviving patients). There was no statistically significant difference in the primary endpoint of local–regional failure (LRF) rate between the treatment arms. The 3-year LRF rate was 36% for control and 44% for Epo (p = 0.56). There were also no significant differences in local–regional progression-free survival (LRPFS), patterns of failure, overall survival, or toxicity. The 3-year LRPFS rate was 52% for control and 47% for Epo. The overall survival rate was 57% and 56%, respectively. Conclusions: The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes. The study was not specifically designed to detect a potential negative association between Epo and tumor progression/survival. [Copyright &y& Elsevier]

Abstract: Background and purpose: Changes in tumor size during the course of radiotherapy warrant performing adaptive radiotherapy (ART). This work investigates the feasibility and usefulness of acquiring on-board cone-beam CT (CBCT) for ART for patients with bulky head and neck tumors treated with IMRT and for prostate patients with potentially significant target position variations during the treatment course. Materials and methods: A phantom designed for CT quality assurance was used to compare the dosimetric and geometric accuracy between conventional CT and CBCT from a linear accelerator’s on-board imager. Patient planning CT and CBCT images were acquired before treatment and at mid-course. The IMRT plans made on the CT were applied to the CBCT and dose–volume histograms were calculated. Results: In both phantom and patient studies, the dose–volume histograms (DVHs) based on CBCT images were in excellent agreement with DVHs based on planning CT images. Minimum, maximum and mean doses agreed very well. In a patient study, doses for targets and normal tissues from the same IMRT plans calculated on CBCT images agreed within 1–3% with those calculated on planning CT images. Conclusions: CBCT images can be used to accurately predict dosimetric results. It is feasible to use CBCT to determine dosimetric consequences resulting from tumor shrinkage and patient geometry changes. An additional planning CT may be necessary to perform IMRT re-planning at present in order to accurately delineate tumor and organs. The CBCT has potential to become a very useful tool for on-line ART. [Copyright &y& Elsevier]

The purpose of this study is to assess the real target dose coverage when radiation treatments were delivered to lung cancer patients based on treatment planning according to the RTOG-0236 Protocol. We compare calculated dosimetric results between the more accurate anisotropic analytical algorithm (AAA) and the pencil beam algorithm for stereotactic body radiation therapy treatment planning in lung cancer. Ten patients with non-small cell lung cancer were given 60 Gy in three fractions using 6 and 10 MV beams with 8–10 fields. The patients were chosen in accordance with the lung RTOG-0236 protocol. The dose calculations were performed using the pencil beam algorithm with no heterogeneity corrections (PB-NC) and then recalculated with the pencil beam with modified Batho heterogeneity corrections (PB-MB) and the AAA using an identical beam setup and monitor units. The differences in calculated dose to 95% or 99% of the PTV, between using the PB-NC and the AAA, were within 10% of prescribed dose (60 Gy). However, the minimum dose to 95% and 99% of PTV calculated using the PB-MB were consistently overestimated by up to 40% and 36% of the prescribed dose, respectively, compared to that calculated by the AAA. Using the AAA as reference, the calculated maximum doses were underestimated by up to 27% using the PB-NC and overestimated by 19% using the PB-MB. The calculations of dose to lung from PB-NC generally agree with that of AAA except in the small high-dose region where PB-NC underestimates. The calculated dose distributions near the interface using the AAA agree with those from Monte Carlo calculations as well as measured values. This study indicates that the real minimum PTV dose coverage cannot be guaranteed when the PB-NC is used to calculate the monitor unit settings in dose prescriptions. [ABSTRACT FROM AUTHOR]

Purpose: To determine efficacy and toxicities of postoperative concurrent chemoradiation using docetaxel in high-risk head and neck cancer. Methods and Materials: High-risk patients were enrolled 2–8 weeks after surgery. Treatment included 60 Gy for 6 weeks with weekly docetaxel 25 mg/m2 and erythropoietin alpha 40,000 U for hemoglobin ≤12 g/dL. Primary endpoints included locoregional control (LC), disease-free survival (DFS), and patterns of failure (POF). Secondary endpoints were toxicity and quality of life. Results: Eighteen patients were enrolled (14 male, 4 female), aged 24–70 years (median, 55 years). Primary site included oropharynx = 7, oral cavity = 8, hypopharynx = 1, and larynx = 2. Pathologic American Joint Committee on Cancer Stage was III = 3 patients, IV = 15 patients. High-risk eligibility included ≥2 positive lymph nodes = 13, extracapsular extension = 10, positive margins = 8 (11 patients with two or more risk factors). Docetaxel was reduced to 20 mg/m2/week after 5 patients had prolonged Grade 3 or higher mucositis. Overall, number of doses delivered was 2 of 6 = 1, 3 of 6 = 2, 4 of 6 = 2, 5 of 6 = 4, 6 of 6 = 9 patients. With median follow-up of 30 months (range, 5–66), 10 (56%) patients are alive and have no evidence of disease (NED); POF: three local recurrences (two with distant) and 1 distant only. One-year survival was 76%, median PFS and DFS had not been reached. Three-year LC was 82%. No Grade 3 or higher late toxicities were observed, although a few cases of prolonged mucositis and taste loss (>3 months) were seen, particularly at 25 mg/m2/week. Conclusion: Postoperative radiation therapy with weekly docetaxel 20 or 25 mg/m2/week for high-risk postoperative head and neck cancer caused intolerable mucosal toxicity, prompting early study termination. Further studies should consider 15 mg/m2. Actuarial 3-year LC is 82%, similar to cisplatin-based chemoradiation regimens. Distant metastasis remains an important issue requiring additional systemic interventions. [Copyright &y& Elsevier]